Pharmacogenetics of the Effects of Colesevelam on Colonic Transit in Irritable Bowel Syndrome with Diarrhea
Background Protein products of klothoβ ( KLB ) and fibroblast growth factor receptor 4 ( FGFR4 ) impact fibroblast growth factor 19-mediated feedback inhibition of hepatic bile acid (BA) synthesis. Variants of KLB and FGFR4 influence colonic transit (CT) in diarrhea-predominant irritable bowel syndr...
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Published in | Digestive diseases and sciences Vol. 57; no. 5; pp. 1222 - 1226 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.05.2012
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Background
Protein products of klothoβ (
KLB
) and fibroblast growth factor receptor 4 (
FGFR4
) impact fibroblast growth factor 19-mediated feedback inhibition of hepatic bile acid (BA) synthesis. Variants of
KLB
and
FGFR4
influence colonic transit (CT) in diarrhea-predominant irritable bowel syndrome (IBS-D).
Aim
The purpose of this study was to test the hypothesis that colesevelam’s slowing effects on CT in IBS-D patients is influenced by genetic variants in
KLB
and
FGFR4
.
Methods
We examined pharmacogenetic effects of
KLB
and
FGFR4
coding variants (SNPs) on scintigraphic CT response to the BA sequestrant, colesevelam 1.875 g b.i.d. versus placebo (PLA) for 14 days in 24 female IBS-D patients.
Results
FGFR4
rs351855 and
KLB
rs497501 were associated with differential colesevelam effects on ascending colon (AC) half-emptying time (
t
1/2
,
P
= 0.046 and
P
= 0.085 respectively) and on overall CT at 24 h (geometric center, GC24:
P
= 0.073 and
P
= 0.042, respectively), with slower transit for rs351855 GA/AA (but not for GG) and rs497501 CA/AA (but not CC) genotypes.
Conclusion
FGFR4
rs351855 and
KLB
rs4975017 SNPs may identify a subset of IBS-D patients with beneficial response to colesevelam. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0163-2116 1573-2568 |
DOI: | 10.1007/s10620-012-2035-5 |